The Causes of Klinefelter Syndrome and How it Affects Men

Klinefelter Syndrome can cause infertility in men, as well as other health issues. What are the causes of Klinefelter Syndrome? What are the symptoms? Learn more in this article.
The Causes of Klinefelter Syndrome and How it Affects Men

Last update: 22 August, 2021

Klinefelter Syndrome is characterized by chromosomal abnormalities that lead to the development of primary hypogonadism. Since these symptoms are related to low sperm production, early treatment is usually successful. So, what are the causes of Klinefelter Syndrome?

There is a lot of uncertainty surrounding this condition.

For that reason, we will be telling you everything you need to know about it in this article.

Common symptoms of Klinefelter Syndrome

The symptoms of Klinefelter Syndrome can vary depending on your age group. These symptoms become far more evident after puberty when low testosterone levels are more apparent.

Klinefelter syndrome in babies

Since babies haven’t yet reached puberty, symptoms are rare and even tend to go unnoticed. Unless the baby’s symptoms are very evident, the condition may go undiagnosed.

In this age group, you may see muscle weakness and delayed psychomotor development. When pediatricians give infants their routine check-ups, they pay particular attention to the age at which they acquire certain motor skills.

This includes being able to hold their heads up, their first words, and the first time they can grasp small objects on their own, among other firsts. To do this, professionals often use a clinical scale called the Denver test, which assesses both gross and fine motor skills. 

On occasion, some babies may suffer from cryptorchidism. This is a common condition that is characterized by defects in the drop of the testicles towards the scrotum. Initially, from an embryological point of view, the testicles are in the abdominopelvic cavity.

Since the treatment for this condition involves surgery, doctors tend to wait some time to see if the testicles will descend on their own. If that doesn’t happen, then they will need to intervene. If not, it will lead to fertility problems, something that is already common with Klinefelter Syndrome.

A baby crying

Klinefelter syndrome in children and adolescents

Symptoms begin to become more noticeable during and after puberty. At that stage, patients will see noticeable differences between themselves and fellow students or relatives. The low production of male sex hormones can partly explain this.

Parents tend to start getting worried and call the pediatrician, if they notice excessive growth, especially in the legs. Another sign is increased breast tissue development, making them similar to those of women (gynecomastia).

In almost all cases, testicle development is minimal. Their size remains almost unchanged throughout their adolescent years. Consequently, the child will not either not have pubic hair or other common signs of puberty, or they will be delayed.

Social, psychological, and communicative problems may also appear at this age. Many patients suffer from dyslexia, as well as shyness and a lot of insecurities. It’s not clear if this is a direct or indirect consequence of hormonal disorders.

According to the Klinefelter Syndrome Association (KSA), when all of these factors are combined, it can result in poor school performance, sometimes caused by bullying.

Klinefelter syndrome in adults

At this stage, the symptoms are much more evident and infertility is one of the biggest problems. In fact, many patients go to the doctor in the first place to address this issue, which could result in a late diagnosis.

There are several causes of infertility. However, with Klinefelter Syndrome, it is the result of low or no sperm count. These are the male sex cells, which are vital for successful fertilization.

In addition, adults will see low development of muscle tissue, even with weight training. And, in severe cases, it can lead to osteoporosis.

Patients with Klinefelter Syndrome are also at an increased risk of developing malignant neoplasms, especially breast cancer and lymphomas. Sometimes, other tumors can appear as well.

In this case report, published in 2019, a 42-year-old male patient was admitted to a hospital facility. The report states that the hospital admitted him with a respiratory infection along with a space-occupying injury to the chest.

The patient’s data revealed a history of fertility problems, well-above-average height, testicular atrophy, and gynecomastia, among other changes. This led to a laboratory-confirmed diagnosis of Klinefelter Syndrome.

Later, they performed a thoracic lesion biopsy. The report from this biopsy showed that it was a thymoma. This is a neoplasm that develops from the cells of the thymus. The thymus is an organ involved in the development of the immune system and that tends to disappear over time.

The causes of Klinefelter Syndrome

Klinefelter Syndrome is caused by a set of chromosomal changes. These changes, depending on the severity and the number of affected cells in the body, will cause varying symptoms.

The information contained within genes is organized into structures called chromosomes, and they are present in many living organisms. In the case of human beings, there are 23 pairs of chromosomes in all cells, except sex cells. These cells have half the number.

When fertilization takes place, the type of chromosomes determine the sex of the individual. Women have two X chromosomes (XX), while men have one X and one Y (XY). These acronyms refer to the form they take when viewed in the laboratory.

Patients with Klinefelter Syndrome have a genetic defect in which they have two X chromosomes and one Y chromosome (XXY). This is known as “aneuploidy.” There are other less common variations, such as the XXXY and XXXXY patterns.

The causes of Klinefelter syndrome: Can you pass it on to children?

Even though this is a genetic problem, it isn’t hereditary. The risk of a patient with this disease having children with the same condition is equal to that of the general population. This condition is entirely random.

According to a publication by the Spanish Association of Pediatrics, the risk of recurrence is around 1%, especially in older mothers. This means that couples who have a child with the disease are more likely (although still low) of having another child with the syndrome.

Risk factors

As we already mentioned, this disease appears sporadically and randomly in the general population. As of right now, the only mild risk factor in the development of this disease is advanced maternal age (over 40 years).

However, having Klinefelter Syndrome is in itself a cardiovascular risk factor, according to this article. Several studies have determined this due to a higher prevalence of certain conditions, such as:

  • Mitral valve prolapse
  • Arrhythmias
  • Cardiac malformations, such as atrial or ventricular communication, and tetralogy of Fallot
  • Venous ulcers and thromboembolic risk

The first of these conditions results in a clinical issue known as mitral regurgitation. It’s characterized by an inadequate closure of this valve, which communicate the atrium with the left ventricle. These are two chambers of the heart that handle oxygenated blood and pump it to the rest of the body.

Thromboembolic risk can lead to the development of deep vein thrombosis and pulmonary thromboembolism. These conditions can be immediately life threatening. To detect these diseases, there are some warning signs to keep in mind.

How do doctors diagnose it?

During a medical evaluation, the specialist may suspect this condition if your medical history includes some of the symptoms we mentioned above. However, before doing specific tests to diagnose the disease, they usually do other tests to look for more common causes of Klinefelter Syndrome.

The latter tests look for the sex hormone levels in the blood and a karyotype. The first tests measure testosterone, follicle stimulation hormone (FSH) and luteinizing hormone (LH).

The last two hormones are usually high, while testosterone levels are low. This can lead to a diagnosis of primary hypogonadism, a condition that defines this syndrome. With this condition, the testes are incapable of producing testosterone.

Chromosomal analysis is determined by a karyotype. In this technique, they separate and observe the chromosomes. This allows for easy identification of any of the aforementioned anomalous genetic patterns, especially XXY.

Also, the doctor will need a blood sample. The doctor will remove the patient’s T lymphocytes and will analyze the genetic material within the cell nucleus using special stains. Even though erythrocytes or red blood cells are more abundant, and are easily accessible, they don’t use them for these tests because they don’t have a nucleus.

Doctors can also perform these tests during pregnancy in the case of older mothers, or those at risk of developing other chromosomal malformations. The test uses a sample of cells that are in the amniotic fluid.

A man talking.

What treatments exist?

Klinefelter Syndrome doesn’t have a cure. Still, there are some therapeutic measures that help to reduce symptoms. For example, hormone replacement therapy with testosterone.

Since people with this syndrome have low levels of testosterone, they may benefit from treatment during puberty. That’s why early diagnosis is so vital. This can help with the development of male sexual characteristics to an extent.

Treatment of infertility is more complicated, especially since many patients don’t seek treatment until adulthood. This is when the testes’ have difficulty creating sperm.

In these cases, assisted reproductive techniques are a valid and highly effective option. One of the methods is “intracytoplasmic sperm injection.” This includes extracting the sperm (if the patient has any) and inserting them into the partner’s eggs.

The rest of the symptoms require specific treatments, which different specialists will carry out. For example, mood disorders will require psychotherapy, poor performance will require evaluation by a school counselor, and gynecomastia could be treated by a surgeon with tissue removal. 

Tips and recommendations

Once a professional has made the diagnosis, it’s important to follow the doctor’s instructions regarding hormone replacement therapies or symptomatic treatment, if necessary.

Psychological support is vital, since problems associated with bullying, insecurities, depression or dysthymia could hurt the patient more than they physical problems or infertility.

What you should remember about Klinefelter Syndrome

Klinefelter Syndrome is a genetic condition specialists link with various hormonal and psycho-affective disorders. Although there’s no cure, it’s necessary to go to a specialist so they can evaluate the symptoms. Early diagnosis could help the patient maintain their quality of life. Prompt treatment can reduce many of its sequelae.

Various specialists can make the diagnosis, depending on age and context. Normally, the most common doctors that work with this condition are pediatricians, family doctors, interns, and endocrinologists.

It might interest you...
What Do Sex Hormones Do?
Step To HealthRead it in Step To Health
What Do Sex Hormones Do?

In addition to controlling the development of secondary characteristics, sex hormones participate in multiple functions in your body, like bone gro...



  • Bojesen A, Juul S & Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. The Journal of Clinical Endocrinology and Metabolism 2003; 88: 622–626.
  • Bojesen A, Stochholm K, Juul S, and Gravholt CH. Socioeconomic Trajectories Affect Mortality in Klinefelter Syndrome. J Clin Endocrinol Metab 96:2098–2104, 2011.
  • Ji J, Zöller B, Sundquist J, Sundquist K. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort
    study. Int J Cancer 2016; 139: 754-8.
  • López, J. Síndrome de Klinefelter. Rev Esp Endocrinol Pediatr 2014;5 Suppl(1):85-90.
  • Oates RD. The natural history of endocrine function and spermatogenesis in Klinefelter syndrome: what the data show. Fertility and Sterility 2012;98:266-273.
  • Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN 2009 Successful fertility treatment for Klinefelter’s syndrome. J Urol 182:1108–1113.